LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat

被引：112

作者：

Schmidt, Elena ^{[1
,2
]}

Dhaouadi, Ines ^{[1
,2
]}

Gaziano, Isabella ^{[1
,2
]}

Oliverio, Matteo ^{[1
,2
]}

Klemm, Paul ^{[1
,2
]}

Awazawa, Motoharu ^{[1
,2
]}

Mitterer, Gerfried ^{[3
]}

Fernandez-Rebollo, Eduardo ^{[4
,5
]}

Pradas-Juni, Marta ^{[1
,2
,4
]}

Wagner, Wolfgang ^{[5
]}

Hammerschmidt, Philipp ^{[1
,2
]}

Loureiro, Rute ^{[1
,2
,4
]}

Kiefer, Christoph ^{[4
]}

Hansmeier, Nils R. ^{[1
,2
]}

Khani, Sajjad ^{[1
,2
]}

Bergami, Matteo ^{[2
]}

Heine, Markus ^{[6
]}

Ntini, Evgenia ^{[7
]}

Frommolt, Peter ^{[2
]}

Zentis, Peter ^{[2
]}

Orom, Ulf Andersson ^{[8
]}

Heeren, Joerg ^{[6
]}

Blueher, Matthias ^{[9
]}

Bilban, Martin ^{[3
,10
]}

Kornfeld, Jan-Wilhelm ^{[1
,2
,4
]}

机构：

[1] Max Planck Inst Metab Res, Gleueler Str 50, D-50931 Cologne, Germany

[2] Cellular Stress Responses Ageing associated Dis C, Cologne Cluster Excellence, Joseph Stelzmann Str 26, D-50931 Cologne, Germany

[3] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria

[4] Univ Southern Denmark, Dept Biochem & Mol Biol BMB, Campusvej 55, DK-5230 Odense M, Denmark

[5] Rhein Westfal TH Aachen, Med Sch, Helmholtz Inst Biomed Engn Stem Cell Biol & Cellu, Pauwelstr 20, D-52074 Aachen, Germany

[6] Inst Biochem & Mol Cell Biol, Martinistr 52, D-20246 Hamburg, Germany

[7] Max Planck Inst Mol Genet, Ihnestr 63-73, D-14195 Berlin, Germany

[8] Aarhus Univ, Inst Mol Biol & Genet, CF Mollers 3, DK-8000 Aarhus C, Denmark

[9] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany

[10] Med Univ Vienna, Core Facil, A-1090 Vienna, Austria

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧洲研究理事会;

关键词：

LONG NONCODING RNAS; ADIPOSE-TISSUE; MITOCHONDRIAL DYSFUNCTION; INSULIN; DIFFERENTIATION; NETWORK; METHYLATION; RECEPTOR; ADIPOCYTES; EVOLUTION;

D O I：

10.1038/s41467-018-05933-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Increasing brown adipose tissue (BAT) thermogenesis in mice and humans improves metabolic health and understanding BAT function is of interest for novel approaches to counteract obesity. The role of long noncoding RNAs (IncRNAs) in these processes remains elusive. We observed maternally expressed, imprinted IncRNA H19 increased upon cold activation and decreased in obesity in BAT. Inverse correlations of H19 with BMI were also observed in humans. H19 overexpression promoted, while silencing of H19 impaired adipogenesis, oxidative metabolism and mitochondrial respiration in brown but not white adipocytes. In vivo, H19 overexpression protected against DIO, improved insulin sensitivity and mitochondrial biogenesis, whereas fat H19 loss sensitized towards HFD weight gains. Strikingly, paternally expressed genes (PEG) were largely absent from BAT and we demonstrated that H19 recruits PEG-inactivating H19-MBD1 complexes and acts as BAT-selective PEG gatekeeper. This has implications for our understanding how monoallelic gene expression affects metabolism in rodents and, potentially, humans.

引用

页数：16

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